Skin is composed of a top layer, the epidermis, which is approximately 20 cell layers or about 0.1 mm in thickness, and a lower layer, the dermis, which is from about 1 to about 4 mm in thickness and contains small blood vessels, collagen, elastin and fibroblasts. The dermis provides structural support and nutrients to the epidermis. Aging has been shown to increase cellular heterogeneity of the epidermal layer, however, it has little effect on the thickness of the epidermal layer. The supporting dermis, on the other hand, is known to thin with age and exposure to the sun and environmental contaminants. The dermal layer provides the support and blood supply for the epidermis, therefore the dermal layer is important in maintaining the elasticity and appearance of the skin. Disruption of the supporting dermis leads directly to sagging and consequent furrowing of the epidermis, i.e., the formation of wrinkles.
Deep wrinkles are also due to continual stretching and contraction of both the dermis and epidermis. Currently, these deep wrinkles or furrows may only be eliminated by plastic surgery or by collagen injections directly beneath the depressed areas. The fine wrinkles that occur with age and prolonged exposure to the sun and other environmental contaminants are the direct result of deterioration of the supporting dermal layer. Other environmental effects on the skin are discussed in U.S. Pat. Nos. 4,938,969 and 5,140,043.
As a result of the aging process and damage caused by incident radiation, a disruption of the collagen bundles that provide support to the epidermis is observed. Collagen exists normally in dense, organized patterns. During the aging process collagen becomes disorganized and less supportive of the epidermis and the dermis loses elasticity. There is also progressive loss of circulatory support from the small blood vessels that are more numerous and close to the surface in young skin. The result of aging on skin, whether or not it has been accelerated by incident radiation, is a deterioration of the dermal layer—fewer fibroblasts, less collagen, less elastin and less circulatory support. Consequently, the normal stretching and contraction of the skin leads to damage of the dermis that is not readily corrected and wrinkling results.
Dermatologists and cosmetologists have directed their efforts to improving the appearance of skin using agents known to stimulate the growth and proliferation of epidermal cells. Newly proliferated cells provide more structure and hold more moisture, giving the skin a younger appearance. One method of causing new skin cell proliferation is accomplished by use of an irritant or chemical peel in which the uppermost layers of the epidermis are caused to slough off, leading to proliferation and replacement with new epidermal cells. While such treatment is recognized to provide some cosmetic improvement, it does not address the major causative factor, namely, the compromised supporting dermal layer.
Considerable effort has also been expended to find ways to prevent adverse changes in the skin brought about by ultraviolet (UV) exposure. Preventative approaches include physically blocking or absorbing the UV radiation before it can enter the skin using UV absorbing compounds. Blocking and absorbing are effective but are cumbersome because sun blockers or absorbers must be applied before every exposure and may be washed off with water. For example, after swimming UV absorbing compounds must typically be reapplied. Further, the long-term side effects of many of the compositions containing sun blockers and/or absorbers are not known.
L-ascorbic acid has many known biological functions from enzymatic cofactor to “sparing” agent against vitamin E depletion. See, for example, Englard and Seifter, “The Biochemical Functions of Ascorbic Acid,” Ann. Rev. Nutri. 6:365-406, (1986); Kunert and Tappel, “The Effect of Vitamin C on in vivo Lipid Peroxidation in Guinea Pigs as Measured by Pentane and Ethane Production, Lipids 18:271-74 (1983). The latter function of L-ascorbic acid may partly account for its “anti-oxidant” status. Additionally, at higher concentrations, ascorbic acid is known to react with both the super oxide and hydroxyl radicals. The super oxide, and the hydrogen peroxide and hydroxyl radical subsequently generated, are oxygen-containing free radicals now known to be generated in vivo under a variety of normal and pathological conditions. These radicals have been implicated as causative agents for everything from sunburn to aging and are believed to destroy lipid membranes, break down DNA and inactivate enzymes, among other effects. An immense amount of work has been done in the last two decades documenting the deleterious behavior of oxygen radicals. Several recent texts on the subject include: Oxy-radicals in Molecular Biology & Pathology, D Cerutti, 1. Fridovich, J. McCord, eds., (Alan R. Liss, Inc. New York, 1988); Biological Role of Reactive Oxygen Species in Skin, 0. Hayaishi, S. Inamura, Y. Mayachi, eds. (Elsevier Press, New York, 1987); Free Radicals, Aging and Degenerative Diseases, J. E. Johnson, Jr., R. Walford, D. Harmon, J. Miguel, eds. (Alan Liss, Inc., New York, 1986); Free Radicals in Biology and Medicine, B. Halliwell and J. M. C. Gutteridge, eds., (Clarendon Press, Oxford, 1985); and Oxidative Stress Helmut Sies, ed. (Academic Press, 1985). Also addressing the subject are several symposia, including “Oxygen Radicals and Tissue Injury” Proceedings from an Upjohn Symposium (April, 1987); and “Oxygen Free Radicals,” Proceedings from National Heart, Lung & Blood Institute (National Institute of Health, Washington, D.C., December 1987).
As a result of the known effects of the use of ascorbic acid on damaged and aging skin, there are now various Vitamin C or ascorbic acid ointments, serums and creams that are used with varying degrees of success to prevent and/or repair damage to the skin's dermal layer. For example, it has been reported that a composition including ascorbic acid, tyrosine and a non-toxic zinc salt, preferably zinc sulfate, in a vehicle suitable for topical application, when applied to areas showing the fine wrinkles associated with aging/sun exposure, results in a readily perceivable diminution of the fine wrinkle structure. It has also been reported that ascorbic acid topical aqueous compositions are unstable unless maintained at a pH below about 3.5. Topical compositions containing a carrier and a concentration of L-ascorbic acid above about 1% (w/v) may be stable if maintained at a pH below about 3.5 or even below about 2.5.
In addition to ameliorating skin damaged by age or environmental insult, topical ascorbic acid formulations may also exhibit some effectiveness in the treatment of various inflammatory skin maladies such as, for example, inflammatory rosacea, allergic inflammations and hypersensitivity. A few cases in which a topical formulation of ascorbic acid, zinc and tyrosine was applied to rosacea, for example, a slight improvement was observed with long-term use. Such formulations, however, have not been shown to clear up rosacea to a substantial extent and even slight improvement requires long-term, diligent daily application to the affected skin. Improved formulations of topical ascorbic acid are needed to effectively and quickly treat skin maladies such rosacea, allergic inflammations and hypersensitivity.
Currently available ascorbic acid compositions and methods fail to provide the delivery system for formulations having the desired combination of efficacy, non-irritability, stability and convenient storage solutions for topical Vitamin C applications. A significant problem of current compositions is that it is not practical to use more than 15% (w/v) ascorbic acid in a serum, cream gel or other suitable topical formulation for cosmetic use because the low inherent pH (circa 2-2.5) of such a formulation is often quite irritating to the skin. The breakdown of the ascorbic acid in such low pH formulations due to exposure to water, heat, and air can also lead to undesirable discoloration and eventually loss of efficacy. Furthermore, if the ascorbic acid is formulated in a cream with limited water content to enhance stability of the ascorbic acid over time, changes in heat, atmospheric pressure and/or moisture content may activate the ascorbic acid, leading to unacceptable expansion and even explosion of the containers holding such creams or gels. There is, therefore, a continuing need for topical ascorbic acid-based compositions that improve the efficacy and stability of such skin treatment formulations.